Featured Research

from universities, journals, and other organizations

An easier way to control genes

Date:

September 3, 2013

Source:

Massachusetts Institute of Technology

Summary:

Researchers have shown that they can turn genes on or off inside yeast and human cells by controlling when DNA is copied into messenger RNA -- an advance that could allow scientists to better understand the function of those genes.

Share This

MIT researchers have shown that they can turn genes on or off inside yeast and human cells by controlling when DNA is copied into messenger RNA -- an advance that could allow scientists to better understand the function of those genes.

Related Articles

The technique could also make it easier to engineer cells that can monitor their environment, produce a drug or detect disease, says Timothy Lu, an assistant professor of electrical engineering and computer science and biological engineering and the senior author of a paper describing the new approach in the journal ACS Synthetic Biology.

"I think it's going to make it a lot easier to build synthetic circuits," says Lu, a member of MIT's Synthetic Biology Center. "It should increase the scale and the speed at which we can build a variety of synthetic circuits in yeast cells and mammalian cells."

The new method is based on a system of viral proteins that have been exploited recently to edit the genomes of bacterial and human cells. The original system, called CRISPR, consists of two components: a protein that binds to and slices DNA, and a short strand of RNA that guides the protein to the right location on the genome.

"The CRISPR system is quite powerful in that it can be targeted to different DNA binding regions based on simple recoding of these guide RNAs," Lu says. "By simply reprogramming the RNA sequence you can direct this protein to any location you want on the genome or on a synthetic circuit."

Lead author of the paper is Fahim Farzadfard, an MIT graduate student in biology. Samuel Perli, a graduate student in electrical engineering and computer science, is also an author.

Targeting transcription

In previous studies, CRISPR has been used to snip out pieces of a gene to disable it or replace it with a new gene. Lu and his colleagues decided to use the CRISPR system for a different purpose: controlling gene transcription, the process by which a sequence of DNA is copied into messenger RNA (mRNA), which carries out the gene's instructions.

Transcription is tightly regulated by proteins called transcription factors. These proteins bind to specific DNA sequences in the gene's promoter region and either recruit or block the enzymes needed to copy that gene into mRNA.

For this study, the researchers adapted the CRISPR system to act as a transcription factor. First, they modified the usual CRISPR protein, known as Cas9, so that it could no longer snip DNA after binding to it. They also added to the protein a segment that activates or represses gene expression by modulating the cell's transcriptional machinery.

To get Cas9 to the right place, the researchers also delivered to the target cells a gene for an RNA guide that corresponds to a DNA sequence on the promoter of the gene they want to activate.

The researchers showed that once the RNA guide and the Cas9 protein join together inside the target cell, they accurately target the correct gene and turn on transcription. To their surprise, they found that the same Cas9 complex could also be used to block gene transcription if targeted to a different part of the gene.

"This is nice in that it allows you do to positive and negative regulation with the same protein, but with different guide RNAs targeted to different positions in the promoter," Lu says.

'A lot of flexibility'

The new system should be much easier to use than two other recently developed transcription-control systems based on DNA-binding proteins known as zinc fingers and transcription activator-like effector nucleases (TALENs), Lu says. Although they are effective, designing and assembling the proteins is time-consuming and expensive.

"There's a lot of flexibility with CRISPR, and it really comes from the fact that you don't have to spend any more time doing protein engineering. You can just change the nucleic acid sequence of the RNAs," Lu says.

The researchers also designed the transcription-control system so that it can be induced by certain small molecules that can be added to the cell, such as sugars. To do this, they engineered the genes for the guide RNAs so that they are only produced when the small molecule is present. Without the small molecule, there is no guide RNA and the targeted gene is undisturbed.

This type of control could be useful for studying the role of naturally occurring genes by turning them on and off at specific points during development or disease progression, Lu says.

Lu is now working on building more advanced synthetic circuits to perform applications such as making decisions based on several inputs from a cell's environment. "We'd like to be able to scale this up and demonstrate the most complex circuits that anyone's ever built in yeast and mammalian cells," he says.

The research was funded by the Defense Advanced Research Projects Agency, the National Institutes of Health New Innovator Award and the National Science Foundation.

More From ScienceDaily

More Health & Medicine News

Featured Research

Mar. 31, 2015  Babies receiving poor nutrition in the womb tend to be smaller at birth, which has been linked to the development of obesity and other health problems later in life. Researchers continue to discover ... full story

Mar. 31, 2015  In addition to their physical injuries, women who are victims of domestic violence are also at a greater risk of mental health problems such as depression and psychotic symptoms. "We studied the ... full story

Mar. 31, 2015  New research has scientists re-thinking how a lethal fungus grows and kills immune cells. The study hints at a new approach to therapy for Candida albicans, one of the most common causes of ... full story

Mar. 31, 2015  As the United States faces transplant waiting lists that continue to grow longer over time, there is increasing debate about the proper way to incentivize living donations. Due to organ shortages, ... full story

Mar. 31, 2015  The most virulent strains of Streptococcus suis, the leading cause of bacterial meningitis in adult humans in parts of southeast Asia and in pigs around the world, are likely to have evolved and ... full story

Mar. 31, 2015  A unique pattern of immune molecules in the cerebrospinal fluid of people with myalgic encephalomyelitis/chronic fatigue syndrome have been discovered, providing insights into the basis for cognitive ... full story

Mar. 31, 2015  Children who get a taste of their parents' wine now and then may be more likely than their peers to start drinking by high school, according to a new report. The findings are based on 561 Rhode ... full story

Mar. 31, 2015  Scientists have uncovered the unique mechanism of a powerful natural product with wide-ranging antifungal, antibacterial, anti-malaria and anti-cancer effects. The work sheds light on the natural ... full story

Mar. 30, 2015  Neuroscientists are taking inspiration from natural motor control to design new prosthetic devices that can better replace limb function. Researchers have tested a range of brain-controlled devices ... full story

Mar. 30, 2015  Scientists have found the genetic signature of enterovirus D68 in half of the California and Colorado children diagnosed with acute flaccid myelitis -- sudden, unexplained muscle weakness and ... full story

Featured Videos

Solitair Device Aims to Takes Guesswork out of Sun Safety

Reuters - Innovations Video Online (Mar. 31, 2015)  The Solitair device aims to take the confusion out of how much sunlight we should expose our skin to. Small enough to be worn as a tie or hair clip, it monitors the user&apos;s sun exposure by taking into account their skin pigment, location and schedule. Matthew Stock reports.
Video provided by Reuters

Soda, Salt and Sugar: The Next Generation of Taxes

Washington Post (Mar. 30, 2015)  Denisa Livingston, a health advocate for the Dinι Community Advocacy Alliance, and the Post&apos;s Abby Phillip discuss efforts around the country to make unhealthy food choices hurt your wallet as much as your waistline.
Video provided by Washington Post

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015)  Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17
Video provided by AFP

Apr. 11, 2011  Although it has been many years since the human genome was first mapped, there are still many genes whose function we do not understand. Researchers from Sweden and Canada have teamed up to produce ... full story

Dec. 5, 2010  Scientists have made an unexpected finding about the method by which certain genes are activated. Contrary to what researchers have traditionally assumed, genes that work with other genes to build ... full story

July 23, 2010  For the first time, researchers have shown that they can deliver those same reprogramming genes using RNA, the genetic material that normally ferries instructions from DNA to the cell's ... full story

June 5, 2010  With the rapid and continuous advances in biotechnology, scientists are better able to see inside the nucleus of a cell to unlock the secrets of its genetic material. However, what happens outside of ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.